Renal protective effects and mechanisms of the angiotensin receptor-neprilysin inhibitor LCZ696 in mice with cardiorenal syndrome.

Life Sciences
Ying LiGuangping Li

Abstract

This study investigated the renal protective effects and mechanisms of angiotensin receptor-neprilysin inhibitor LCZ696 in mice with cardiorenal syndrome. Mice were divided into abdominal aortic ligation alone, or treatment with LCZ696 or valsartan, whilst those undergoing sham surgery served as controls. Rat proximal renal tubular epithelial cells from the NRK-52E line were treated with control solution, LCZ696 or valsartan, in the presence or absence of Ang II for 24 h. Compared to controls, abdominal aortic ligation significantly increased plasma NT-proBNP and urine neutrophil gelatinase-associated lipocalin (NGAL), which were associated with reduced renal length and velocity time integral on ultrasonography. Histology revealed wrinkling of the glomerular capillary wall and sclerosis of the glomerulus, dilatation of the Bowman's capsule, accompanied by diffuse renal tubular atrophy and fibrosis, accompanied by lower kidney index and higher percentage area of fibrosis. Increases in NGAL and decreased ANP protein and mRNA expression levels were observed. These abnormalities were significantly prevented by LCZ696 and to a lesser extent by valsartan. Cellular experiments demonstrated a central role of Ang II/transforming growth ...Continue Reading

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Citations

Aug 17, 2021·Naunyn-Schmiedeberg's Archives of Pharmacology·Rasha M S M MohamedDalia M Abd El Motteleb

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